Otitis media is a pathological condition common to humans, and most common to children. During episodes of otitis media, fluid accumulates in the middle ear or, as it is also known, the tympanic cavity.
Acute otitis media is a condition in which fluid accumulation in the middle ear is accompanied by signs or symptoms of ear infection (including both viral and bacterial etiologies). Such pathology may exhibit a bulging eardrum accompanied by pain or, in some instances, perforation of the tympanic membrane. Such perforations may also be accompanied by drainage of purulent material. In contrast, otitis media with effusion, also known as serous otitis media, is typified by fluid accumulation within the tympanic cavity without signs of infection.
Both acute otitis media and otitis media with effusion may cause substantial pain as pressure increases, positively or negatively, within the confines of the tympanic chamber. Antibiotics, steroids, and antibiotics in combination with steroids have been utilized to treat otitis media. Antihistamine/decongestants have also been utilized in the treatment of otitis media with effusion.
The anatomical features of the middle ear define what can be described as a sealed chamber. On its lateral border, the middle ear is effectively isolated from the external auditory meatus (in the absence of a punctured ear drum), by the intact tympanic membrane. Medially, the middle ear is effectively sealed from the inner ear by a bony wall. The posterior wall of the tympanic cavity communicates with a large, but effectively sealed mastoid antrum. Only the anterior wall of the middle ear contains a passageway for effective communication outside of the tympanic cavity. There, a natural pathway provided by the auditory or, as it is also known, the eustachian tube, provides communication with the nasopharynx. The eustachian tube is normally closed, sealing the middle ear/mastoid chamber, and opens at intervals to equalize pressure between the nasopharynx and middle ear.
During episodes of acute otitis media, the painful increased middle ear pressure may naturally resolve through a resultant perforation of, and drainage through, the tympanic membrane. However, such perforation is unusual and the increased fluid pressure associated with otitis media with effusion does not resolve via this mechanism. In fact, for those patients suffering otitis media for prolonged periods of time, (three months or more) and especially for those evidencing significant associated hearing loss, myringotomy with the placement of a tympanostomy is indicated as a means of equalizing middle ear pressure and in order to restore normal hearing. Unfortunately, during episodes of otitis media with effusion (OME), a time when the natural pathway and pressure relief functions of the eustachian tube would be most useful, the increase pressure required to open the lumen (as described in more detail above and below), effectively eliminates this means of relieving middle ear pressurization. Reduced patency of the eustachian tube is believed to be one of the primary causes of OME in pediatric patients. In fact, it is known that OME elevates eustachian tube opening pressure independent of other pathological conditions effecting this conduit. U.S. Pat. No. 6,616,913 (Sep. 9, 2003) (“THE '913 patent”) discloses a method of increasing and enhancing mammalian eustachian tube lumen patency and pressure equalization performance by administering an aerosolized mixture of lipid crystals comprised of a mixture of one or more lipids surfactants and one or more spreading agents selected from the group consisting of cholesteryl esters, phospholipids, carbohydrates, and proteins, in powder form, and one or more fluorocarbon propellants through a mammalian nasal orifice. Upon administration, the propellant(s) are evaporated from the mixture and the lipid crystals are deposited and, through the action of the spreading agent, reach the pharyngeal terminus of the eustachian tube. As the lipid crystals come into contact with luminal surfaces of the eustachian tube, an amorphous spread film is formed thereupon substantially decreasing the opening pressure of the lumen. Pathologic conditions such as otitis media, are effectively treated by decreasing eustachian tube opening pressure as a pathway for release of the pressurized contents of the middle ear is provided via the proper physiologic opening and depressurization function of the eustachian tube lumen so as to quickly relieve the pain caused by such pressure while also promoting resolution of the subject infection. The '913 patent also disclosed incorporation of a therapeutically active agent effective in the treatment of otitis media added to the mixture of lipid crystals. Upon administration of said aerosol mixture, the amorphous spread film formed thereby carries said therapeutically active agent through the eustachian tube to the tissues of the middle ear so as to effectively treat the underlying pathologic condition. (See U.S. Pat. No. 6,616,913, abstract)
The '913 patent teaches the use of a metered dose nasal administration device to deliver the subject mixture of lipid crystals, both with and without a therapeutically active agent, to the eustachian tube via the nasopharyngeal orifice thereof. As stated in the '913 patent, a mixture of one or more lipids and one or more spreading agents selected from the group consisting of cholesteryl esters, phospholipids, carbohydrates, and proteins, all in powder form, and one or more fluorocarbon propellants is first prepared. The lipids and the spreading agents are advantageously selected to be insoluble in the propellants. The lipids utilized in practicing the method of the present invention are present in an amount of about 80 to 99.5 percent by weight and the spreading agents are present in an amount of about 0.5 to about 20 percent by weight, both based upon the total weight of the mixture. Combination of the one or more lipids, one or more spreading agents and one or more fluorocarbon propellants results in the formation of lipid crystals and described in more detail, below. A metered dose of the mixture of lipid crystals is then administered, via an external nasal orifice into a mammal upon which the present method is practiced.
The '913 patent discloses application of the subject mixture of lipid crystals via a metered dose nasal administration device so as to more closely control dose administration. However, without means of delivering a focused stream of lipid crystals through the nasal orifice to the eustachian tube and a means of targeting the pharyngeal orifice of the auditory tube with such a focused stream, a significant portion of the mixture is ineffectively applied to other mucosal surfaces. Administration of the aerosolized lipid crystals through the nasal orifice utilizing administration devices of the prior art devoid of a means of targeting the eustachian tube and/or focusing the stream of crystals administered thereby results in, at best, an indiscriminate, shotgun-like deposition of said crystals upon the mucosal surfaces of the sinus passages and sinus airways. The mucosal surfaces of these airways and sinuses demonstrate an air/liquid interface formed by the secretion of muco- and muco-serous secretions thereupon.
Upon deposition of the lipid crystals upon these mucosal surfaces, said crystals form a uniform and amorphous spread film and effectively reduce the surface tension thereupon. (See U.S. Pat. No. 6,616,913, col 6, lines 40-43). Although it would be expected that such an indiscriminate application would allow the surfactant/spreading agent to eventually spread to and flow into the eustachian tube's pharyngeal orifice, the above-described delivery devoid of any targeting means would not be optimal or capable of efficient, rapid and selective application.
Ordinarily, and, as shown in many commercials, advertisements, drug inserts and other media, patients, and those applying medications to patients utilizing nasal administration devices, utilize such devices in such a way as to direct the spray provided thereby in a relative upward direction towards the patient's ethmoid with no particular or provided targeting guidance. This is the natural and expected mode of use of such devices in the vast majority of prior art nasal administration and inhalation techniques as such devices were intended to dispense compounds to the tissues of the nose, the sinuses or, in other instances, to a large portion of the respiratory system via inhalation—without any intended discrete area of application—. For such applications, utilizing a nasal administration device in the usual upward direction, or, for that matter, with no particular direction whatsoever, was perfectly acceptable. Equally acceptable for application of medications not intended for a discrete application to a structure—such as the eustachian tube orifice—, was a shotgun-like dispersion of medicine provided by the devices of the prior art. Simply put, in the prior art, the medications carried by such devices were never intended for specific and or discrete areas. However, in regard to the lipid crystals discussed above, or, for that matter, any other compositions, compounds or medications—specifically intended for application to the eustachian tube or middle ear via nasal administration, such incorrect or random application is expected to reduce the speed, efficiency and optimum effect otherwise provided by precise targeting of the nasopharyngeal orifice of the auditory tube.
More specifically, at the present time, there is no known negative effect resulting from application of a portion of the above-discussed lipid crystals (disclosed in the '913 patent) to the mucosa lining the sinuses and upper respiratory surfaces rather than limiting application to the mucosa directly adjacent to the nasopharyngeal opening of the eustachian tube. However, such applications, in the form of a mis-directed and unfocused medication delivery, would be expected to require a greater amount of medication and a greater amount of time to take effect as much of the composition would be applied to areas quite distant from the eustachian tube's pharyngeal orifice. Certainly, a large portion of a haphazardly applied unfocused stream of such medication would result in a greater amount so dispensed never reaching the eustachian tube. Thus, it would be highly advantageous if a nasal administration device could be designed, arranged and configured to deliver the aforementioned crystals, or, any mixture intended for delivery to the eustachian tube and/or middle ear—via the eustachian tube—, in a substantially focused (collimated) and targeted manner to the mucosal lining of the nasopharynx adjacent the pharyngeal orifice of the eustachian tube. It would be still further advantageous if a method and device could be disclosed to administer a well collimated stream of said lipid crystals from a device which included a means of providing accurate positioning of the device so that a collimated stream delivered thereby would be directed to the region of the nasopharynx in close proximity to the eustachian tube orifice.